The analysis of cancer within complex heterogeneous tissues represents special challenges posed by the presence of infiltrating non-neoplastic cells. We have developed biolithography, a novel and proprietary method (U.S. Pat. No. 6,159,681 to Syntrix, Inc.) for high-resolution tissue microdissection that employs lithography directly on biologic samples. Biolithography offers several advantages over laser-based methods that include improvements in spatial resolution, reliability, and contamination risk. Importantly, there is the potential for simplified and less costly instrumentation because the method requires only low-energy incoherent light. In this Phase I/II FAST-TRACK proposal, we propose to develop an automated biolithography system that will integrate the advantages of biolithography within an automated system that offers both attractive performance and cost characteristics. The automated biolithography system will consist of a novel PhotoBlaster instrument that projects user-defined microscopic light patterns during biolithography using low-energy incoherent light and a silicon chip-based microdisplay device. Consumables will consist of adhesive polypropylene reaction wells and validated reagents and photofilms suitable for isolating DNA, RNA and protein from microscopic regions of interest. Phase I is designed to prove the feasibility of the proposed PhotoBlaster design to generate photopatterns of sufficient intensity and minimum feature size. The Phase II program will yield a final system prototype. The proposed automated system of biolithography offers the potential to provide a facile and cost-effective method to address whole organism analysis for a wide audience of researchers and clinicians engaged in cancer analysis. Syntrix will commercialize the PhotoBlaster system that results from this research either through direct sales or through third-parties.